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Biomedical subjects

V Demicheli

Publications and source records attributed to V Demicheli.

At least 19 recordsLinked to original sources

Neuraminidase inhibitors for preventing and treating influenza in healthy adults.

BACKGROUND: Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in interpandemic years and in a pandemic. OBJECTIVES: To assess the effects of NIs in preventing or ameliorating influenza, its transmission and its complications in healthy adults and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2004 to September, Week 4 2005), EMBASE (2003 to June 2005) and contacted manufacturers, researchers in the field, and authors of studies evaluated in the review. SELECTION CRITERIA: Randomised or quasi-randomised placebo-controlled studies of NIs in healthy adults exposed to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: Two authors applied inclusion criteria, assessed trial quality and extracted data. We structured the comparisons into prophylaxis, treatment and adverse events with further subdivision by outcome and dose. MAIN RESULTS: We identified four prophylaxis, 13 treatment and four post-exposure prophylaxis (PEP) trials. In prophylaxis compared to placebo, NIs have no effect against influenza-like illnesses (ILI) (relative risk (RR) 1.28, 95% confidence interval (CI) 0.45 to 3.66 for oral oseltamivir 75 mg daily; RR 1.51, 95% CI 0.77 to 2.95 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (RR 0.39, 95% CI 0.18 to 0.85), or 73% (RR 0.27, 95% CI 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (RR 0.38, 95% CI 0.17 to 0.85). Neither NI has a significant effect on asymptomatic influenza. Oseltamivir induces nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for PEP has an efficacy of 58.5% (15.6% to 79.6) for households and of 68% (34.9 to 84.2%) to 89% in contacts of index cases. Zanamivir has similar performance. The hazard ratios for time to alleviation of influenza symptoms were in favour of the treated group 1.33 (1.29 to 1.37) for zanamivir and 1.30 (1.13 to 1.50) for oseltamivir. Viral nasal titres were significantly diminished by both NIs. Oseltamivir 150 mg daily prevented lower respiratory tract complications (OR 0.32, 95% CI 0.18 to 0.57). We could find no comparative data on the effects of oseltamivir on avian influenza. AUTHORS' CONCLUSIONS: Because of their low effectiveness, NIs should not be used in routine seasonal influenza control. In a serious epidemic or pandemic, NIs should be used with other public health measures. We are unsure of the generalisability of our conclusions from seasonal to pandemic or avian influenza.

Acetamides↗

Vaccines for preventing influenza in the elderly.

BACKGROUND: Influenza vaccination of elderly individuals is recommended worldwide and has been targeted toward the elderly and those at serious risk of complications. OBJECTIVES: Our aim was to review the evidence of efficacy, effectiveness and safety of influenza vaccines in individuals aged 65 years or older. SEARCH STRATEGY: We searched the following databases on The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness (Issue 1, 2006); MEDLINE (January 1966 to March Week 3 2006); EMBASE (Dialog 1974 to 1979; SilverPlatter 1980 to December 2005); Biological Abstracts (SilverPlatter 1969 to December 2004); and Science Citation Index (Web of Science 1974 to December 2004). SELECTION CRITERIA: We considered randomised, quasi-randomised, cohort and case-control studies assessing efficacy against influenza (laboratory-confirmed cases) or effectiveness against influenza-like illness (ILI) or safety. Any influenza vaccine given independently, in any dose, preparation or time schedule, compared with placebo or with no intervention was considered. DATA COLLECTION AND ANALYSIS: We grouped reports first according to the setting of the study (community or long-term care facilities) and then by level of viral circulation and vaccine matching. We further stratified by co-administration of pneumococcal polysaccharide vaccine (PPV) and by different types of influenza vaccines. We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications and deaths. MAIN RESULTS: Sixty-four studies were included in the efficacy / effectiveness assessment, resulting in 96 data sets. In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against ILI was 23% (6% to 36%) and non-significant against influenza (RR 1.04: 95% CI 0.43 to 2.51). We found no correlation between vaccine coverage and ILI attack rate. Well matched vaccines prevented pneumonia (VE 46%; 30% to 58%), hospital admission (VE 45%; 16% to 64%) and deaths from influenza or pneumonia (VE 42%, 17% to 59%). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19; 95% CI 0.02 to 2.01), ILI (RR 1.05: 95% CI 0.58 to 1.89), or pneumonia (RR 0.88; 95% CI 0.64 to 1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%; 12% to 38%) and all-cause mortality (VE 42%; 24% to 55%). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%; 21% to 33%), respiratory diseases (VE* 22%; 15% to 28%) and cardiac disease (VE* 24%; 18% to 30%); and for all-cause mortality (VE* 47%; 39% to 54%). The public health safety profiles of the vaccines appear to be acceptable. AUTHORS' CONCLUSIONS: In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest. The apparent high effectiveness of the vaccines in preventing death from all causes may reflect a baseline imbalance in health status and other systematic differences in the two groups of participants.

Aged↗

Influenza vaccination for healthcare workers who work with the elderly.

BACKGROUND: Healthcare workers (HCW) (nurses, doctors, other health professionals, cleaners and porters), have substantial rates of clinical and sub-clinical influenza during influenza seasons and may transmit influenza to those in their care, especially the vulnerable elderly. OBJECTIVES: To identify and summarise comparative studies assessing the effects of vaccinating healthcare workers (HCW) on the incidence of influenza, influenza-like-illness (ILI) and its complications on elderly residents in long-term facilities. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews and the NHS Database of Abstracts of Reviews of Effectiveness (DARE) (The Cochrane Library Issue 1, 2006); MEDLINE (January 1966 to Week 1, February 2006); EMBASE (1974 to March 2006); Biological Abstracts (1969 to December 2004); and Science Citation Index-Expanded (1974 to March 2006). SELECTION CRITERIA: Comparative randomised and non-randomised studies reporting the effects of influenza vaccines on the incidence of viral infections in institutions for the elderly of any type, in any schedule of vaccination given to HCW caring for elderly residents of long-term facilities aged 60 years or older. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality using criteria from the Cochrane Reviewers' Handbook and the Newcastle-Ottawa scale (for non-randomised studies). MAIN RESULTS: We included two cluster randomised controlled trials (C-RCT) and one cohort study. Staff vaccination appears to have significant effect against ILI (absolute vaccine efficacy (VE) 86%, 95% confidence interval (CI) 40% to 97%) only when patients are vaccinated too; if patients are not vaccinated, staff immunisation shows no effect (based on one C-RCT). Based on a small number of observations from two C-RCTs, the vaccines have no efficacy against influenza (odds ratio (OR) 0.86, 95% CI 0.44 to 1.68) or lower respiratory tract infections (OR 0.70, 95% CI 0.41 to 1.20) but were effective against deaths from pneumonia (VE 39%, 95% CI 2% to 62%) and deaths from all causes (VE 40%, 95% CI 27% to 50%). All findings must be interpreted with caution given the presence of selection bias. AUTHORS' CONCLUSIONS: We concluded that there is no credible evidence that vaccination of healthy people under the age of 60, who are HCWs caring for the elderly, affects influenza complications in those cared for. However, as vaccinating the elderly in institutions reduces the complications of influenza and vaccinating healthy persons under 60 reduces cases of influenza, those with the responsibility of caring for the elderly in institutions may want to increase vaccine coverage and assess its effects in well-designed studies.

Adult↗

Impact of immigration and HIV infection on tuberculosis incidence in an area of low tuberculosis prevalence.

The aim of this study is to assess the effects of immigration from countries with a high prevalence of tuberculosis (HPCs), of HIV/AIDS prevalence, and the ageing of the indigenous population, on tuberculosis distribution in a low-prevalence area (LPCs), the Piedmont Region of Italy. Tuberculosis incidence and HIV cases were identified by linking records from the surveillance systems. Overall, 640 tuberculosis cases were identified and crude annual incidence was found to be 17.3/100000. The incidence rate ratio for HIV infection as a risk factor for tuberculosis (11.4 and 51.9 among individuals from HPCs and LPCs respectively) was greater than that for immigration from HPCs (6.7 and 30.9 among HIV+ and HIV- individuals). Immigration accounted for a larger number of incident cases [population attributable risk % (PAR %): 31.8 and 52.8% among HIV+ and HIV- individuals] than did HIV infection (PAR %: 5.4 and 11.1% among individuals from HPCs and LPCs). Efforts should be made to identify and treat young immigrants from HPCs.

AIDS-Related Opportunistic Infections↗

Amantadine and rimantadine for influenza A in adults.

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the efficacy, effectiveness and safety ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to August Week 4, 2005), EMBASE (October 2003 to July 2005) and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control medication or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prophylaxis (prevention) trials the numbers of participants with clinical influenza (influenza-like-illness or ILI) or with confirmed influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever, length of hospital stay and adverse effects. MAIN RESULTS: Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.2). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prophylaxis were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine. Neither drug affected the rate of viral shedding from the nose and the course of asymptomatic influenza. AUTHORS' CONCLUSIONS: Amantadine and rimantadine have comparable efficacy and effectiveness in relieving or treating symptoms of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine. The effectiveness of both drugs in interrupting transmission is probably low. Routine use of both drugs should be discouraged and both drugs should only be used when all other measures fail.

Adult↗

Antivirals for influenza in healthy adults: systematic review.

BACKGROUND: Use of antivirals is recommended for the control of seasonal and pandemic influenza. Our aim was to review the evidence of efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults. METHODS: We searched various Databases to October, 2005, and contacted manufacturers and corresponding authors. We included randomised controlled trials comparing prophylactic (n=27) or treatment (n=27) efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For treatment trials, because of inconsistent and non-standardised reporting, we expressed continuous outcomes either as means or as hazard ratios. FINDINGS: We included 51 reports of 52 randomised controlled trials. Amantadine prevented 61% (95% CI 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like illness, but caused nausea (OR 2.56, 1.37-4.79), insomnia and hallucinations (2.54, 1.50-4.31), and withdrawals because of adverse events (2.54, 1.60-4.06). There was no effect on asymptomatic cases (RR 0.85, 0.40-1.80). In treatment, amantadine significantly shortened duration of fever compared with placebo (by 0.99 days, -1.26 to -0.71), but had no effect on nasal shedding of influenza A viruses (0.93, 0.71-1.21). The fewer data for rimantadine showed comparable effects. In prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1.28, 0.45-3.66 for oral oseltamivir 75 mg daily, 1.51, 0.77-2.95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1.79, 1.10-2.93), especially at higher prophylactic doses (2.29, 1.34-3.92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58.5% (15.6-79.6) for households and from 68% (34.9-84.2) to 89% (67-97) in contacts of index cases. In influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1.33, 1.29-1.37 for zanamivir; 1.30, 1.13-1.50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference -0.62, -0.82 to -0.41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0.32, 0.18-0.57). We could find no credible data on the effects of oseltamivir on avian influenza. INTERPRETATION: The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public-health measures.

Adolescent↗

Vaccines for preventing influenza in healthy children.

BACKGROUND: In children and adults the consequences of influenza are mainly absences from school and work, however the risk of complications is greatest in children and people over 65 years old. OBJECTIVES: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children; assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness) and document adverse events associated with receiving influenza vaccines. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005); OLD MEDLINE (1966 to 1969); MEDLINE (1969 to December 2004); EMBASE (1974 to December 2004); Biological Abstracts (1969 to December 2004); and Science Citation Index (1974 to December 2004). We wrote to vaccine manufacturers and a number of corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years old. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Fifty-one studies involving 263,987 children were included. Seventeen papers were translated from Russian. Fourteen RCTs and 11 cohort studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live vaccines showed an efficacy of 79% (95% confidence interval (CI) 48% to 92%) and an effectiveness of 33% (95% CI 28% to 38%) in children older than two years compared with placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% (95% CI 41% to 71%) than live vaccines but similar effectiveness: 36% (95% CI 24% to 46%). In children under two, the efficacy of inactivated vaccine was similar to placebo. Thirty-four reports containing safety outcomes were included, 22 including live vaccines, 8 inactivated vaccines and 4 both types. The most commonly presented short-term outcomes were temperature and local reactions. The variability in design of studies and presentation of data was such that meta-analysis of safety outcome data was not feasible. AUTHORS' CONCLUSIONS: Influenza vaccines are efficacious in children older than two years but little evidence is available for children under two. There was a marked difference between vaccine efficacy and effectiveness. That no safety comparisons could be carried out emphasizes the need for standardisation of methods and presentation of vaccine safety data in future studies. It was surprising to find only one study of inactivated vaccine in children under two years, given recent recommendations to vaccinate healthy children from six months old in the USA and Canada. If immunisation in children is to be recommended as public-health policy, large-scale studies assessing important outcomes and directly comparing vaccine types are urgently required.

Adolescent↗

Influenza vaccination for health-care workers who work with elderly people in institutions: a systematic review.

Our aim was to review the evidence of efficacy and effectiveness of influenza vaccination of health-care workers in reducing cases of influenza-like illness, influenza, complications from influenza, death from influenza, and death from all causes among the elderly people they care for in institutions. We searched 11 electronic databases in any language and identified two cluster-randomised controlled trials with moderate risk of bias and one cohort study at high risk of bias that addressed our questions. Staff vaccination had a significant effect on influenza-like illness (vaccine effectiveness [VE] 86%, 95% CI 40-97%) only when patients were vaccinated too. If patients were not vaccinated, staff immunisation had no effect. Vaccinating health-care workers did not appear efficacious against influenza (RR 0.87, 95% CI 0.46-1.63). There was no significant effect of vaccination on lower respiratory tract infections: (RR 0.70, 95% CI 0.41-1.20). Deaths from pneumonia were significantly reduced (VE 39%, 95% CI 2-62%), as were deaths from all causes (VE 40%, 95% CI 27-50%). These findings must be interpreted in the light of possible selection, performance, attrition, and detection biases.

Aged↗

Vaccines for women to prevent neonatal tetanus.

BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant and/or non-pregnant women with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. OBJECTIVES: To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2004) , The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004). We also used the results from handsearching and consultations with manufacturers and authors. SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion, data extraction and trial quality. MAIN RESULTS: Two trials (10,560 infants) were included. One study (1919 infants) assessed the effectiveness of tetanus toxoid in preventing neonatal tetanus deaths. After a single dose, the relative risk (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two or three dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at 4 to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). AUTHORS' CONCLUSIONS: Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.

Adult↗

Vaccines for measles, mumps and rubella in children.

BACKGROUND: Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine, and the resultant drop in vaccination rates in several countries, persists despite its almost universal use and accepted effectiveness. OBJECTIVES: We carried out a systematic review to assess the evidence of effectiveness and unintended effects associated with MMR. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to December 2004), EMBASE (1974 to December 2004), Biological Abstracts (from 1985 to December 2004), and Science Citation Index (from 1980 to December 2004). Results from reviews, handsearching and from the consultation of manufacturers and authors were also used. SELECTION CRITERIA: Eligible studies were comparative prospective or retrospective trials testing the effects of MMR compared to placebo, do-nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age. These studies were carried out or published by 2004. DATA COLLECTION AND ANALYSIS: We identified 139 articles possibly satisfying our inclusion criteria and included 31 in the review. MAIN RESULTS: MMR was associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, and similar incidence of other adverse effects compared to placebo. The vaccine was likely to be associated with benign thrombocytopenic purpura, parotitis, joint and limb complaints, febrile convulsions within two weeks of vaccination and aseptic meningitis (mumps) (Urabe strain-containing MMR). Exposure to MMR was unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps) (Jeryl-Lynn strain-containing MMR). We could not identify studies assessing the effectiveness of MMR that fulfilled our inclusion criteria even though the impact of mass immunisation on the elimination of the diseases has been largely demonstrated. AUTHORS' CONCLUSIONS: The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with MMR cannot be separated from its role in preventing the target diseases.

Adolescent↗

Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review.

BACKGROUND: Influenza vaccination of elderly individuals is recommended worldwide. Our aim was to review the evidence of efficacy and effectiveness of influenza vaccines in individuals aged 65 years or older. METHODS: We searched five electronic databases to December, 2004, in any language, for randomised (n=5), cohort (n=49), and case-control (n=10) studies, assessing efficacy against influenza (reduction in laboratory-confirmed cases) or effectiveness against influenza-like illness (reduction in symptomatic cases). We expressed vaccine efficacy or effectiveness as a proportion, using the formula VE=1-relative risk (RR) or VE*=1-odds ratio (OR). We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications, and deaths. FINDINGS: In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against influenza-like illness was 23% (95% CI 6-36) and non-significant against influenza (RR 1.04, 0.43-2.51). Well matched vaccines prevented pneumonia (VE 46%, 30-58) and hospital admission (VE 45%, 16-64) for and deaths from influenza or pneumonia (VE 42%, 17-59), and reduced all-cause mortality (VE 60%, 23-79). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19, 0.02-2.01), influenza-like illness (RR 1.05, 0.58-1.89), or pneumonia (RR 0.88, 0.64-1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%, 12-38) and all-cause mortality (VE 42%, 24-55). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%, 21-33), respiratory diseases (VE* 22%, 15-28), and cardiac disease (VE* 24%, 18-30), and for all-cause mortality (VE* 47%, 39-54). INTERPRETATION: In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest.

Aged↗

Methodological issues arising from systematic reviews of the evidence of safety of vaccines.

Adaptations to the recognized methods of systematic reviewing are required when addressing questions about safety, particularly about rare and/or long-term serious adverse events. Conducting a systematic review of vaccine safety requires the implementation of novel strategies for locating studies, the use of experimental instruments to assess the quality of non-randomized studies, and the employment of pooling methods for non-randomized data, where appropriate. Standardizing both the indexing of adverse event data on electronic libraries and their reporting would improve the potential of systematic reviews of vaccine to draw accurate conclusions about the safety of a vaccine.

Data Interpretation, Statistical↗

Amantadine and rimantadine for preventing and treating influenza A in adults.

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but these drugs are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the effectiveness and safety ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to November week 2, 2003), EMBASE (January 1990 to September 2003) and the reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinical influenza (influenza-like-illness or ILI), i.e. confirmed influenza A, and adverse effects were analysed. Analysis for treatment trials included the mean duration of fever and length of hospital stay, and the number of adverse effects. MAIN RESULTS: Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWERS' CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine causes fewer adverse effects than amantadine.

Adult↗

Vaccines for preventing influenza in healthy adults.

BACKGROUND: Three different types of influenza vaccines are currently produced worldwide. None is traditionally targeted to healthy adults. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has negative impact on the vaccines acceptance and uptake. OBJECTIVES: To assess the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to December 2003); and EMBASE (1990 to December 2003). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Twenty five reports of studies involving 59,566 people were included. The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza by 48% (95% confidence interval (CI) 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 70% (95% CI 56% to 80%). The yearly recommended vaccines had low effectiveness against clinical influenza cases: 15%(95% CI 8% to 21%) and 25% (95% CI 13% to 35%) respectively. Overall the percentage of participants experiencing clinical influenza decreased by 6%. Use of the vaccine significantly reduced time off work but only by 0.16 days for each influenza episode (95% CI 0.04 to 0.29 days); Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. REVIEWERS' CONCLUSIONS: Influenza vaccines are effective in reducing serologically confirmed cases of influenza. However, they are not as effective in reducing cases of clinical influenza and number of working days lost. Universal immunisation of healthy adults is not supported by the results of this review.

Adult↗

Influenza vaccines in adults.

Available influenza vaccines contain inactivated viruses, either whole or in parts, and are administered parenterally or intranasally. Their composition varies yearly because of viral antigenic shifts and drifts. Vaccines with a composition matching yearly World Health Organization recommendations are 72% [95% confidence interval (CI) = 54-83%] efficacious (prevention of influenza cases caused by influenza viruses A and B). Their effectiveness [capacity to prevent clinical influenza, or influenza-like illness (ILI)] is lower, at 37% (95% CI = 18-52%). A decision to vaccinate an adult population has to take into account the efficacy of the vaccines and their effectiveness (the likely proportion of ILI caused by influenza A and B viruses, amenable to prevention by vaccination), as well as costs and likely compliance. As the yearly levels of circulating A and B viruses are difficult to predict during the decision time for a vaccination campaign, there is a considerable element of uncertainty regarding the likely effectiveness of 'this year's' vaccine.

Adolescent↗